The term “prion” is used to describe proteinaceous-infectious agents that cause relatively similar brain diseases in humans and/or in animals, which are invariably fatal. These diseases are generally referred to as transmissible spongiform encephalopathies (TSEs). TSEs include Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD) in humans, bovine spongiform encephalopathy (BSE) in cattle (also known as “mad cow disease”), scrapie in sheep, and wasting disease in elk. All of these diseases attack the neurological organs of humans and/or animals which are susceptible to the diseases. They are characterized by initially long incubation times followed by a short period of neurological symptoms, including dementia and loss of coordination, and eventually death.
The infectious agent responsible for these diseases is believed to be a simple protein with no associated nucleic acids. The pathogenic mechanism for such prion diseases is proposed to involve an initially normal host encoded protein. A prion is actually a normal host encoded protein (PrP) that exists in a first conformational state in a non-infected host. The protein undergoes a conformational change to a second, abnormal conformational state, which has the ability of self-propagation. For example, a normal host encoded protein may exist in a first conformational state PrPc (cellular) in a non-infected host and then change to a second conformational state, such as PrPSc (in the disease scrapie), in infected hosts. Despite being chemically similar to each other, the abnormal prion form differs from the normal host encoded protein with respect to higher-order structure (i.e., secondary, tertiary, and/or quaternary structure) and solubility. With scrapie, for example, one difference between the scrapie form (PrPSc) and the cellular form is in the secondary structure of α-helixes as compared to β-pleated sheets. PrPSC has a higher β-pleated sheet content compared to the normal cellular prion protein structure.
The exact cause or reason for the change from the normal conformational state to the abnormal (infected) conformational state is, at present, unknown. The abnormal form of the protein is not broken down effectively in the body and its accumulation in certain tissues (in particular neural tissue) eventually causes tissue damage, such as cell death. Once significant neural tissue damage has occurred, the clinical signs are observed.
Prion diseases may thus be classified as a protein aggregation disease, which also includes several other fatal diseases, such as Alzheimer's disease and amyloidosis. In the case of CJD, the most prevalent prion disease in humans, about 85% of cases are thought to arise sporadically, about 10% are thought to be inherited, and about 5% arise iatrogenically. Associated diseases may also include haemozoin precipitation during malarial parasite infection.
Although not considered to be highly contagious, prion diseases can be transmitted by certain high-risk tissues, including the brain, spinal cord, cerebral spinal fluids, and the eye. Iatrogenic transmission has been reported during several procedures, including dura-mater grafting, corneal transplants, pericardial homografts, and through human gonadotropin and human growth hormone contamination. Problems with blood transmission have been reported.